Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and predominance among the LDL fraction of smaller and denser particles. We report on an FCHL kindred (the M-kindred) in which decreased VLDL and LDL-apoB elimination rates rather than enhanced production rates were the main kinetic abnormalities. Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins (including light and dense LDLs) were determined during placebo and pravastatin treatment periods. Kinetic parameters, as determined from incorporation of stable isotopically labeled amino acids and mass spectrometric analysis, were remarkably similar in the five study subjects during the placebo period, despite their diverse plasma lipid profiles. Compared with nine normo-lipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs) and low LDL-apoB FCRs were observed in every ca se. The FCRs of both LDL subclasses increased with treatment.